Role of CD80 (B7.1) and CD86 (B7.2) in the immune response to an intracellular pathogen.
The costimulatory ligands CD80 and CD86 play a crucial role in the initiation and maintenance of an immune response. We demonstrate that whereas infection of human monocytes with viable tachyzoites of Toxoplasma gondii resulted in rapid induction of expression of CD80 and up-regulation of expression of CD86, incubation with killed organisms failed to alter the levels of expression of these costimulatory ligands. The T. gondii-mediated changes in levels of expression of these molecules are critical to the T cell response to the parasite. Proliferation of resting T cells in response to parasite-infected cells was dependent on both CD80 and CD86. More importantly, early production of IFN-gamma in response to T. gondii by T cells from T. gondii-seronegative individuals occurred only after stimulation with monocytes that exhibited increased expression of CD80 and CD86 (monocytes infected with viable parasites) and was almost completely ablated by the combination of anti-CD80 plus anti-CD86 mAb. Moreover, proliferation and IFN-gamma production by CD4+ CD45RA+ T cells from unexposed individuals were dependent on both CD80 and CD86. These data indicate that pathogen-monocyte interaction influences the ensuing T cell response.
Subauste
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Research Institute, Palo Alto Medical Foundation, CA 94301, USA. subauscs@email.uc.edu
de Waal Malefyt
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D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism / Q000469:parasitology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000502:physiology*; D051940:B7-2 Antigen; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D007424:Intracellular Fluid / Q000276:immunology / Q000469:parasitology; D007700:Kinetics; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor